Standardized swallow challenge medium and method of use for esophageal function testing

ABSTRACT

A swallow challenge medium ( 10 ) is thixotropic for easy swallowing and to provide enough viscosity for effective challenge to peristalsis ( 20 ) and has high ionic density for effective impedance measurements by contact with electrodes ( 41 - 48 ) positioned in a person&#39;s esophagus (E) or oropharynx during swallow testing. The medium ( 10 ) also has a high surface tension so as not to adhere to or coat the electrodes ( 41 - 48 ) or probe ( 12 ) surfaces. These physical characteristics are stabilized and consistent enough to provide standard for esophageal and/or oropharyngeal function testing and diagnostics.

CROSS REFERENCE TO RELATED APPLICATION

[0001] The present application claims priority of U.S. ProvisionalApplication No. 60/443,356, filed Jan. 29, 2003, which application isincorporated herein by reference.

FIELD OF THE INVENTION

[0002] The invention relates generally to assessing esophagealcondition. More particularly, the invention relates to an apparatus andmethod for measuring the movement of a bolus in the esophagus afterswallowing with a swallow challenge medium useful for such measurements.

BACKGROUND OF THE INVENTION

[0003] Accurate measurements of physiological parameters of theesophagus under realistic swallowing conditions are valuable indiagnosing esophageal diseases such as gastroesophageal reflux disease(GERD), abnormal functioning of the lower esophageal sphincter (LES) andperistaltic muscular contractions and movements in the esophagus, andthe like. When a person with a healthy esophagus swallows, circularmuscles in the esophagus contract. The contractions begin at the upperend of the esophagus and propagate downwardly toward the loweresophageal sphincter (“LES”). These muscular contractions are commonlycalled peristaltic movements, contractions, or waves, or simply as“peristalsis”. The function of the peristaltic muscle contractions,i.e., to propel food and drinks through the esophagus to the stomach, issometimes called the motility function, but is also often used to referto peristalsis. Therefore, the terms “motility” or “motility function”and “peristalsis” are sometimes used interchangeably.

[0004] The LES is normally closed, but it opens momentarily, when aperistaltic contraction approaches it, to admit the bolus of food ordrink into the stomach. As a peristaltic contraction passes through eachpoint along the esophagus, the esophageal pressure at that point risesto a maximum and then falls back to a base pressure at the relaxedstate. This peristaltic propagation of the esophageal contraction tendsto propel any swallowed volume of mass, which is called a “bolus”, aheadof the point of peak pressure and down the esophagus toward the stomach.The motility function of the esophagus, i.e., the esophagus' ability tomove a mass, is dependent on several factors, including the peristalticpressure profile and the characteristics of the esophageal muscles.

[0005] Esophageal pressure measurement, or manometry, as well aselectrical impedance have been used to assess motility function of theesophagus and bolus transit dynamics in the esophagus. A typicalesophageal manometer includes an elongated catheter or probe withpressure sensors located along its length. The catheter or probe isdesigned to be inserted into the esophagus, typically reaching the LESand extending into the stomach, of a patient, with the pressure sensorspositioned at the LES and at a plurality of other specific points alongthe length of the esophagus at predetermined distances above the LES.During a typical test, the patient swallows a specific amount of waterwith the manometer placed in the esophagus. The esophageal pressure atthe pressure sensors can be measured and used as an indication of themagnitude and sequence of the peristaltic contractions. In addition,because the positions of the sensors are known, the velocity of theperistaltic motion can also be ascertained from the location of the peakpressure as a function of time. The test can be repeated a number oftimes to obtain a set of pressure and velocity values, a statisticalanalysis of which may be used for diagnostic purposes. For example,according to one protocol, ten 5-ml water swallows are to be performedat approximately 30-second intervals. The patient's functional responseis determined as a percentage of the swallows. For example, a result ofsuch test swallows may show that 80% of the swallows were followed by acontraction pressure of 30 mmHg or greater with an onset velocity ofabout 8 cm/sec, and, therefore, showed normal peristalsis; the remaining20% of the swallows resulted in a contraction pressure of less than 30mmHg and, therefore, are deemed to be ineffective peristalsis.

[0006] While the conventional manometry (pressure measurements) isuseful for assessing certain aspects of the physiology of the esophagus,i.e., peristaltic muscular activity in the esophagus and LES aredetectable as pressure changes, the technique has its limitations in atleast two respects. Esophageal manometry does not measure or predictbolus transit, which is the actual movement of a mass of swallowedmaterial through the esophagus. Esophageal peristalsis generally istriggered by a swallowing action and proceeds whether or not anysubstance is actually swallowed, and the peristaltic muscularcontractions may proceed regardless of whether the bolus is actuallymoving through the esophagus. Further, some swallowed material, such aswater, will flow by gravity through the esophagus, even if there are noperistaltic muscular contractions or if they are irregular or erratic.Thus, the mere manometric detection of propagating peristaltic muscularcontractions, even if they are properly timed and of normal amplitude(strength), does not necessarily mean that any bolus is being propelledby the peristalsis. Thus, incomplete bolus transit may not be detectedby manometry alone. Other substances could be swallowed, such as food,but resulting data, such as impedance, would vary, depending on thecharacteristics of the food or other substances.

[0007] Electrical impedance at a plurality of points in the esophaguscan be used to detect and monitor movement of a bolus through theesophagus. Essentially, a bolus of water or food will have differentelectrical impedance than the non-filled esophagus, so a change inimpedance in the esophagus indicates presence of a bolus. Therefore, anelongated probe positioned in the esophagus with a plurality ofimpedance and/or acidity sensors dispersed along its length can be usedto detect and monitor the bolus transit, i.e., the movement of a bolusthrough the esophagus. Therefore, by combining manometry (pressuremeasurements) with simultaneous impedance measurements, both peristalsisand bolus transit can be quantified, and these measurements, if accurateand dependable, can be combined to determine whether the bolus movementand the peristaltic contractions are in proper synchronization or ifthere is an abnormal or dysfunctional relationship between them.

[0008] Unfortunately, prior to this invention, it was very difficult, ifnot impossible, to get consistent, accurate, reliable, and repeatableimpedance measurements, even if the impedance probes, sensors, andmeasuring equipment, itself, was well-designed and in good workingcondition. The problem was that the swallow media available for suchtests were inadequate. For example, water as a medium for swallow testsprovides very little resistance to peristaltic propulsion and is ofteninadequate to cause esophageal abnormalities to manifest themselvesduring the test. Water also has inconsistent ionic content, varying fromone source to another or from one municipal water system to another,which causes variations in impedance measurements and is ofteninsufficient to even make meaningful impedance measurements. Salinesolution has more ionic content, but it provides insufficient resistanceto peristaltic propulsion to cause esophageal abnormalities to bedetected. Water and saline solution also do not remain in a distinct,well-defined bolus mass and, instead, run and spread by gravity throughthe length of the esophagus, bridging many or all of the impedancesensor electrodes so that sensing distinct bolus transit dynamics inrelation to manometric detection of peristalsis is difficult, if notimpossible. Other substances, such as yogurt, mash potatoes, or otherfoods could be swallowed, but resulting data, such as impedance, wouldvary, depending on the physical characteristics of the foods, such asionic content, viscosity, surface tension, and the like. Also, foodstend to coat or stick to the probe and impedance sensor electrodes onthe probe, even after the bolus has passed, which interferes withsubsequent impedance measurements and makes it difficult and oftenimpossible to detect bolus transit in subsequent swallows. These andother deficiencies contribute to erratic, inconsistent, unreliable, andunrepeatable test results.

[0009] A state-of-the-art technique for observing and assessing actualbolus transit includes a barium esophagram diagnostic test, in which apatient in front of an X-ray camera performs swallows of a contrastmedium that shows distinctly in an X-ray image. This diagnostic method,however, has a number of drawbacks as well, including the high cost ofequipment and exposure of patients to ionizing radiation, and it is notconducive to ambulatory testing. In addition, manometric datasynchronized with bolus transit are not available from barium esophagramtests. Such synchronized data is often important in assessing thecomplex physiology of bolus transit dynamics.

SUMMARY OF THE INVENTION

[0010] The swallow challenge medium of this invention has a number ofadvantages over traditional substances, e.g., water, saline solution,yogurt, mashed potatoes, and other foods, used for manometer andimpedance testing of esophageal motility functions. To be truly usefulin a broad sense, impedance and manometer (pressure) test results foresophageal motility functions and diagnostics should be consistent,dependable, repeatable, and accurate, not only for effective testing onindividual patients, but also so that reliable standards can bedeveloped and so that individual swallow tests can be compared to suchstandards in a meaningful manner and with a meaningful results. Theswallow challenge medium of this invention provides dependable,controllable, and consistent viscosity, conductivity and impedance, andnon-stick, surface tension characteristics to meet these goals with along enough shelf life to remain dependable, consistent, and reliablefor most ordinary users and uses in esophageal testing. It is alsoingestible, food-grade material that is not harmful to humans.

[0011] Generally, according to one aspect of the invention, a swallowchallenge medium is provided, which has a viscosity of about 1,000centipoise to about 100,000 centipoise at 30 rpm when tested using aBrookfield Viscometer, LVT model, with a number-4 spindle. The medium ispreferably, but not necessarily, thixotropic, exhibiting a decrease inviscosity by, for example, about 20-fold or more, over a two-decadeincrease in the rotation velocity of the viscometer spindle. It providesimpedance of about 300 to 500 ohms, thus has conductivity in the rangeof about 4.5 to 7.6 millisiemens/cm (mS/cm). The medium can also have apH of about 3.5 to about 9.0. The challenge medium includes water, athickening agent such as a polysaccharide in general and carrageenan inparticular, and an ion donor such as sodium chloride. It also includespreservatives such as sodium benzoate. All ingredients are food-grade.

[0012] According to another aspect of the invention, the swallowchallenge medium also has very high surface tension so that it has ahigh cohesion (attraction to like molecules) and low adhesion(attraction to unlike molecules), which makes it substantiallynon-sticking to the impedance sensor electrode and probe surfaces.

[0013] According to another aspect of the invention, a method ofmeasuring the physiological functions of an organ includes the followingsteps: (1) introducing a predetermined quantity of a challenge mediuminto the organ, (2) selecting a plurality of pairs of locations along apath in the organ, (3) measuring the impedance between each pair ofpositions, and (4) determining the location of the challenge mediumalong the path as a function of time. The challenge medium can be thechallenge medium described above. The method can also includedetermining the pressure at a plurality of locations along the path inthe organ as a function of time and comparing the location of thechallenge medium along the path with pressure along the path as afunction of time. The method can also include repeating the above stepsa plurality of times and comparing the results with a standard.

[0014] Additional objects, advantages, and novel features of theinvention are set forth in part in the description that follows andothers will become apparent to those skilled in the art upon examinationof the following description and figures or may be learned by practicingthe invention.

BRIEF DESCRIPTION OF THE DRAWINGS

[0015] The accompanying drawings, which are incorporated in and form apart of the specification, illustrate the preferred embodiments of thepresent invention, and together with the written description and claims,serve to explain the principles of the invention. In the drawings:

[0016]FIG. 1 is a diagrammatic illustration, in partiallycross-sectioned elevation, of a swallow challenge medium used inconjunction with an impedance and manometric probe for assessingmotility functions of a person's esophagus;

[0017]FIG. 2 is an enlarged view of the swallow challenge medium in theesophagus adjacent a pair of electric contacts on the probe incombination with a schematic diagram of simple impedance measuringcircuit;

[0018]FIG. 3 is a view similar to FIG. 1, but showing a bolus of theswallow challenge medium moved into position adjacent a first pair ofimpedance sensor electrodes and a pressure sensor on the probe;

[0019]FIG. 4 is a view similar to FIGS. 1 and 3, but with the swallowchallenge medium bolus moved to a position immediately above the loweresophageal sphincter (LES);

[0020]FIG. 5 is a view similar to FIGS. 1, 3, and 4, but with theswallow challenge medium bolus moving through the LES from the esophagusinto the stomach;

[0021]FIG. 6 is a view similar to FIGS. 1 and 3-5, but illustrating anexample of an unsuccessful swallow with the swallow challenge mediumpartially through the LES and partially behind the peristaltic musclecontraction in the esophagus;

[0022]FIG. 7 is a graphical illustration of impedance/time andpressure/time profiles of a normal swallow in relation to a sensorlocation on a probe positioned in a person's esophagus; and

[0023]FIG. 8 is an example of a 4-channel impedance/time profile of aswallow to illustrate functions of this invention.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0024] A swallow challenge medium 10 of this invention is illustrateddiagrammatically in FIG. 1 positioned in a person's esophagus E alongwith a combination impedance and pressure measuring probe 12 on acatheter 14 for monitoring and/or testing motility function of theesophagus E and bolus transit dynamics through the esophagus E. Uponswallowing the swallow challenge medium 10, it forms a bolus in theperson's esophagus E, and a normal esophageal function includesperistaltic muscular contractions 20 of the esophagus wall 16, asillustrated diagrammatically in FIG. 1, to propel the swallow challengemedium (bolus) 10 through the esophagus E to the person's stomach S. Aswill be explained in more detail below, the swallow challenge medium 10provides a bolus that has optimal characteristics to enhance assessmentof motility functions and malfunctions, including establishments ofstandards and comparison of individual cases to such standards.

[0025] One or more pressure sensors 31, 32, 33, 34, 35 and/or aplurality of impedance sensors 41, 42, 43, 44, 45, 46, 47, 48 on theprobe 12 are used to detect and quantify peristalsis and bolus transitdynamics. The pressure sensors, in general, are more suited for useprimarily to detect and quantify peristalsis, and the impedance sensors,in general, are more suited for use primarily to detect and quantifybolus transit dynamics, as will be discussed in more detail below.Therefore, while the most advantageous use of the swallow challengemedium 10 of this invention is with a probe that has both manometer(pressure) and impedance sensing functions, it can, of course, also beused with either a manometer or impedance sensor, separately.

[0026] The catheter 14 and probe 12, themselves, are not part of thisinvention, other than as they are used in combination with the swallowchallenge medium 10 according to this invention. Manometer probes forsuch esophageal peristalsis measurements are well-known in the art andare available from a number of manufacturers. The impedance measuringfeatures are described in U.S. Pat. No. 5,109,870, issued to Silny etal., which is incorporated herein by reference. A combination manometerand impedance catheter and probe is available from Sandhill Scientific,Inc., Highlands Ranch, Colo. Therefore, the pressure and impedancemeasuring capabilities of the probe 12 are described herein only to theextent necessary to explain the salient characteristics of the swallowchallenge medium 10 and how it can be used according to this invention.Suffice it to say, therefore, that the example probe 12 illustrated inFIG. 1 is shown with a plurality of individual pressure sensors 31, 32,33, 34, 35 interspersed with a plurality of impedance sensor contacts41, 42, 43, 44, 45, 46, 47, 48 along a length of the probe section 12 ofthe catheter 14. The pressure sensors 31, 32, 33, 34, 35 are preferablyspaced at known distances apart from each other to facilitatecorrelation of pressures sensed by the sensors 31, 32, 33, 34, 35 tospecific physical locations in the person's esophagus. For example, ifthe pressure sensors 31, 32, 33, 34, 35 are spaced 5 cm apart along thelength of the probe 12, and if the last pressure sensor 35 is positionedin the LES as illustrated in FIG. 1, then it can be assumed thatpressure measurements from the sensors 31, 32, 33, 34 are indicative ofpressures in the esophagus E at 20 cm, 15 cm, 10 cm, and 5 cm,respectively, above the LES. The probe 12 can be positioned in theesophagus E by inserting its distal end 60 and last pressure sensor 35all the way into the stomach S and then pulling it back upwardly untilthe pressure sensor 35 detects the increased pressure that results fromthe pressure sensor 35 being positioned in the lower esophagealsphincter (LES). Of course, other spatial increments or distances canalso be used, and more or fewer pressure sensors can be used, ifdesired. The pressure sensors 31, 32, 33, 34, 35 are connected toappropriate instrumentation, monitor, and display equipment (not shownin FIG. 1), which is also available from manufacturers or suppliers ofthe probes 12 or from other sources known to persons skilled in the art,thus do not need to be described here for an understanding of thisinvention.

[0027] The impedance measurements are facilitated by the plurality ofelectrically conductive contacts or sensors 41, 42, 43, 44, 45, 46, 47,48 dispersed spatially along the probe 12. Impedance, which isopposition to flow of electric current, can be measured between any ofthe contacts or sensors 41, 42, 43, 44, 45, 46, 47, 48, as illustrateddiagrammatically in FIG. 2. While any impedance measuringinstrumentation will work, the simple schematic circuit diagram in FIG.2 illustrates the principle. A constant voltage source 50 is connectedacross a pair of the conductive contacts, e.g., contacts or sensorelements 41, 42, to make an electric current “e⁻” flows between thecontacts or sensor elements 41, 42. The current flow can be measured byan ammeter or similar instrumentation 52. According to Ohm's law, themagnitude of the electric current measured at 52 is proportional to theimpedance of the material through which the electric current “e⁻” flowsbetween the contact or sensor elements 41, 42. Therefore, if the swallowchallenge medium 10 of this invention is positioned across the contactor sensor elements 41, 42 of the probe 12, as illustrated in FIG. 2, theelectric current measured at 52 is dependant at least in part on theimpedance of the swallow challenge medium 10. On the other hand, if theswallow challenge medium 10 is not positioned across the two contacts41, 42, then the current measurement at 52 will be inverselyproportional to the impedance of whatever other material through whichthe current has to flow to complete the electric circuit, such as air,esophageal wall tissue, saliva, or whatever. The lower the impedance ofthe material across the contacts 41, 42, the greater the current flowwill be, and vice versa. Some current control or limiting device orcircuitry 54, represented generically as a resistor in FIG. 2, can beused to prevent the flow of too much electric current, which could bumor otherwise injure the tissue. Of course, the FIG. 2 is only schematic,and the actual wires or conductors used to connect the impedance sensors41, 42, 43, 44, 45, 46, 47, 48 as well as the pressure sensors 31, 32,33, 34, 35 to the instrumentation is routed through the lumen 56 in theprobe 12 and catheter 14 to the exterior of the person's body.

[0028] As mentioned above, the primary function of the pressure sensors31, 32, 33, 34, 35 is to detect and monitor the peristaltic musclecontraction 20 as it progresses down the esophagus E, ideally to propelthe swallow challenge medium 20 through the esophagus E to the stomach(FIG. 1), and the primary function of the impedance sensors 41, 42, 43,44, 45, 46, 47, 48 is to detect and monitor transit of the boluscomprising the swallow challenge medium through the esophagus E to thestomach S. To illustrate, reference is made first to FIG. 1, in whichthe focus of swallow challenge medium 10 is shown positioned in theesophagus E above the first pressure sensor 31 and above the firstimpedance sensor pair 41, 42, where it is being propelled toward thestomach by the peristaltic muscle contraction 20. The LES is shown inFIG. 1 contracted around the probe 12, where the pressure sensor 35 ispositioned near the distal end 60, as explained above. Both the pressuremeasurements and the impedance measurements are just background or baselevels at this point, because both the swallow challenge medium 10 andthe peristaltic muscle contraction 20 are still above the pressuresensors 31, 32, 33, 34, 35 and the impedance sensors 41, 42, 43, 44, 45,46, 47, 48 of the probe 12. Referring now to FIG. 3, where theperistaltic muscle contraction 20 has propelled the swallow challengemedium 10 to a position surrounding the first pair of impedance sensorcontacts 41, 42, and the first pressure sensor 31. Since the swallowchallenge medium 10 is formulated to have a low impedance, as will bediscussed in more detail below, the flow of electric current e⁻(FIG. 2)increases as soon as both sensors 41, 42 are contacted by the swallowchallenge medium 10. Therefore, a decrease in impedance across thesensor contacts 41, 42 detected by the impedance detectorinstrumentation 52 indicates the arrival of the swallow challenge medium10 at the location of the impedance sensor pair 41, 42. Meanwhile, asshown in FIG. 3, the peristaltic muscle contraction 20, which followsthe swallow challenge medium bolus 10, has not yet reached the locationof the first pressure sensor 31, which in the example described above,is about 20 cm above the LES. Therefore, while a decrease of impedanceacross the first pair of sensor contacts 41, 42 indicates the swallowchallenge medium 10 has arrived at the location about 20 cm above theLES, the lack of any simultaneous increase of pressure at the firstpressure sensor 31 indicates that the peristaltic muscle contraction hasnot yet arrived at the location 20 cm above the LES. When thecontraction 20 does arrive at that position, it will apply itscontraction pressure on the pressure sensor 31. Therefore, a pressureincrease detected by pressure sensor 31 will indicate that thecontraction 20 has arrived at that location.

[0029] Next the illustration in FIG. 4 shows that the peristaltic musclecontraction 20 has progressed past the first and second pressure sensors31, 32 to a position at or slightly below the third pressure sensor 33,where it has pushed the swallow challenge medium bolus 10 to a positionjust above the LES. This position of the swallow challenge medium 10 isdetected by the last pair of impedance sensor contacts 47, 48 andpossibly by impedance sensor contacts 46, 47, both of which are alsostill in contact with the swallow challenge medium 10 in this position.Also, the movement of the peristaltic muscle contraction 20 to thisposition is, or just was, detected by the third pressure sensor 33.

[0030] Finally, as illustrated in FIG. 5, as the peristaltic musclecontraction 20 continues to propel the swallow challenge medium 10toward the stomach S, the passing of the contraction 20 would have beendetected by the fourth pressure sensor 34, and the LES opens momentarilyfor the swallow challenge medium bolus 10 to enter the stomach S.

[0031] All of the peristalsis and bolus transit functions describedabove are normal for a healthy esophagus E and LES. However, animportant feature of this invention is to facilitate diagnosis ofdefective or malfunctioning peristalsis and bolus transit and/or LESmalfunctions. One example of this capability is illustrated in FIG. 6,wherein the swallow challenge medium bolus 10 is not transmittedsuccessfully through the LES and into the stomach S before theperistaltic muscle contraction reaches the bottom of the esophagus E andterminates that peristaltic cycle. As illustrated in FIG. 6, there is acondition of bolus stasis in which a portion of the swallow challengemedium bolus 10 is still above the LES as the peristaltic contraction 20by-passes at least the upper portion 62 portion of the bolus 10 insteadof pushing it through the LES and into the stomach S. Therefore, thebolus transit is incomplete. This incomplete bolus transit is detectableby the impedance measurements between sensor contacts 47, 48 and/orsensor contacts 46, 47 still showing the presence of the swallowchallenge medium 10 more than 5 cm above the LES, while the fourthpressure sensor 34 shows that the peristaltic muscle contraction 20 hasalready progressed to within 5 cm of the LES. In other words, thisexample condition indicates that the peristaltic muscle contraction 20is not successfully propelling the bolus 10 through the LES and/or theLES is not admitting the bolus 10 into the stomach. This and otherperistalsis and bolus transit problems can be detected more reliably andin a repeatable manner with the swallow challenge medium 10 of thisinvention than with the use of water, saline solution, or other bolusmaterials, as will be explained in more detail below.

[0032] Another example abnormal pattern (not illustrated), which can bedetected is retrograde bolus movement in which the swallow challengemedium or other bolus moves in a reverse direction, upwardly in theesophagus, after the peristaltic wave passes the bolus. Again, thepressure sensors 31-35 would show passage of the peristaltic wave downthe esophagus, while the impedance sensors 41-48 would show the bolusmoving in the opposite direction. These and other abnormal peristalsisand bolus transit patterns can indicate various disease states orconditions, as will be understood by persons skilled in this art.

[0033] Typical impedance and pressure measurement profiles at onelocation on the probe 12, for example, at the first impedance sensorcontacts 41, 42 and the first pressure sensor 31 about 20 cm above theLES, are shown in FIG. 7 for normal peristalsis and bolus transitsimilar to that illustrated in FIGS. 1 and 2 and described above. Priorto the arrival of the swallow challenge medium bolus 10 at thislocation, the impedance meter 52 (FIG. 2) reads a background or baseimpedance 210 (FIG. 7) from the sensor contact pair 41, 42. Thebackground or base impedance 210 is a function of the conductivity andmass of any esophageal wall tissues, air, or other fluids surroundingand between the electrodes 41, 42. Suitable manometer (pressure meter)instrumentation (not shown) reads the background or base pressure 260(FIG. 7) during this initial time period.

[0034] The person is then instructed to swallow a predetermined amount,for example 5 ml, of the swallow challenge medium 10, which has anelectrical conductivity that is higher than that of the esophagealtissues and other materials that provide the background or baseimpedance 210 discussed above. A particularly advantageous type ofswallow challenge medium 10 according to this invention is described inmore detail below. As the bolus of the swallowed challenge medium 10advances down the esophagus E and passes the first pair of electrodes41, 42, the impedance between the electrodes begins to drop, asindicated at 220 in FIG. 7, approximately when the bolus 10 reaches theupper electrode, i.e., sensor contact 44. Once the bolus of swallowchallenge medium 10 bridges the upper and lower electrodes 41, 42, asshown in FIG. 2, the impedance 230 (FIG. 7) remains substantially at thelowest level 230 until the tail end of the bolus 10 moves beyond theupper electrode 41. The impedance then begins to increase, as indicatedat 240 (FIG. 7) until the bolus 10 is completely detached from bothelectrodes 41, 42, whereupon the impedance returns to the backgroundlevel 210.

[0035] In the meantime, for the pressure sensor 31 located midpointbetween the two electrodes 41, 42 that give rise to the impedance curvein FIG. 7 described above, the background pressure 260 for normalperistalsis prior to and during the time period when the bolus 10 comesinto contact with the electrodes 41, 42, because the muscularcontraction 20 (FIG. 2) of the esophagus E propelling the bolus 10 isstill upstream from the first pressure sensor 31. However, when themuscle contraction 20 passes the first electrode 41 and approaches thepressure sensor 31, the pressure at the pressure sensor 31 begins torise, as indicated at 270 in FIG. 7, at about the same time as therising impedance 240 indicates the bolus 10 is moving away from thatlocation on the probe 12. The pressure reaches its peak 280, when themuscle contraction 20 is at the sensor 31 and then returns to thebackground pressure 260 as the muscle contraction 20 passes beyond thefirst pressure sensor 31.

[0036] Thus, the time profiles of both impedance and pressure, as wellas the timing relationship between the two profiles illustrated in FIG.7 can be used to detect abnormalities of the esophageal motilityfunction. For example, if the impedance at a particular pair, such aselectrodes 41, 42, should ever remain at or near the minimum value 230and not return to the background level for a prolonged period of time(such as beyond the time when a pressure peak 280 is detected at thatlocation or when such a pressure peak 280 is detected by a subsequentpressure sensor 32, 33, or 34 downstream this scenario could be anindication that the peristalsis was ineffective in propelling the bolus10 past the electrodes 41, 42.

[0037] As discussed above, the timing of the pressure peaks 280 detectedat the pressure sensors 31, 32, 33, 34 along the esophagus E can be usedto measure the velocity of peristaltic propagation of the esophagealmuscular contraction 20. Similarly, the timing of the impedance troughs230 detected at successive electrode pairs 41-42, 42-43, 43-44, 44-45,45-46, 46-47, 47-48 (or fewer of these pairs) can be used to measure thevelocity of bolus transit. For example, a set of four impedance/timeprofiles measured on four impedance channels of a probe 12 derived fromfour electrode pairs 41-42, 43-44, 45-46, 47-48, respectively, in aswallow test is shown in FIG. 8. In this example, the pairs ofelectrodes are spaced apart at a center-to-center distance of 5 cm. Theelectrode pairs are numbered 2, 3, 4 and 5, respectively, from theuppermost pair 41-42 to the lowermost pair 47-48. The impedance valuesare labeled, respectively, Z₂, Z₃, Z₄, and Z₅. As seen in FIG. 8, theimpedance trough 310 appears in Z₂ first and progressively later in Z₃(320), Z₄ (330) and Z₅ (340). The time interval 350 between the troughs310, 340 Z₅ and Z₂, i.e., for the bolus 10 to travel the 15 cm from thefirst electrode pair 41-42 and the last electrode pair 47-48, is aboutfive seconds, corresponding to a bolus transit velocity of about 3 cm/s.

[0038] The patient can be instructed to perform a predetermined number(such as ten) of swallows of the swallow challenge medium 10, with theswallows spaced apart by a predetermined amount of time (such as about30 seconds). A statistical analysis can then be performed on the data,and the result compared to a standard to determine whether theesophageal functions of the esophagus E are within or outside normalparameters. For example, if a physician finds that five out of tenswallows by a patent fail to achieve complete transit of the swallowchallenge medium bolus 10 to the stomach S, when the standard for ahealthy esophagus is no more than three out of ten failed bolus transitsfor the type of the particular swallow challenge medium used, thatparticular patient's failure rate may indicate esophageal motilityabnormalities. From the location of the electrode pair that produced theabnormal impedance profile, especially if viewed in relation to theprogression of the peristaltic muscle contractions 20 as monitored bythe pressure sensors 31, 32, 33, 34, 35 as explained above, theapproximate location of a suspect region in the esophagus can also bedetermined. As another example, the bolus transit velocities can also becompared to a standard to assess the condition of the esophagus.

[0039] However, comparing the results of the impedance measurementsand/or pressure measurements with a standard is only meaningful, wherenot only the test conditions, materials, and equipment are standard, butalso where they are designed to bring out or induce a manifestation ofabnormalities that may exist. Test swallows performed with higherviscosity materials provide greater sensitivity to the detection andquantification of abnormal esophageal motility or diseased states.

[0040] As described in more detail below, the invention provides aviscous swallow challenge medium 10 with characteristics that satisfythis requirement as well as other desirable features for use in suchswallow tests for esophageal motility evaluations and diagnostics.

[0041] The swallow challenge medium 10 of this invention issubstantially more viscous than water in order to provide a morevigorous swallow test, but which can still be swallowed without the aidof a liquid by a person with a healthy esophagus. More viscosity alsoprovides a more tightly contained bolus (short length) that keeps theimpedance measurements of the swallow challenge medium 10 more tightlyconfined to fewer of the impedance sensor electrodes 41-48, thusproviding more concise bolus location data at any instant in time. Also,at tighter bolus 10, due to its higher viscosity as well as its highersurface tension, also advances only in response to the propulsive forceof the peristaltic muscle contractions. In contrast, water, for example,flows by gravity and fills the entire length of the esophagus, whichobscures impedance location data and does not challenge the peristalticmuscle contractions in the esophagus. For example, the swallow challengemedium 10 can have a viscosity of about 1,000 to about 100,000centipoise at 30 rpm (i.e., high shear test) using a BrookfieldViscometer, LVT model, with a number-4 spindle, preferably from about5,000 to about 50,000 centipoise, and more preferably from about 6,000to about 20,000 centipoise for comfortable swallows and at leastminimally effective impedance measuring of bolus transit dynamics. It isalso preferred that the viscosity not vary substantially in the shelflife of the swallow challenge medium 10, preferably not more than about15%.

[0042] For such viscosity shelf life stability, especially forpolysaccharide thickening agents, the pH of the swallow challenge medium10 should be in the range of 3.5 to 9.0, preferably about 4.0 to 9.0,and more preferably 4.5 to 8.0. The desired viscosity is largelyachieved and controllable by including a proper amount of thickeningagent and liquid, such as water, in the ingredients. A number of knownfood-grade thickening agents can be used, including polysaccharides,such as carrageenan, jells, or hydrojells.

[0043] It is also preferred, although not essential, that the swallowchallenge medium not only be viscous, but that it also be thixotropic,i.e., that it has a variable viscosity such that it acts more like asolid (higher viscosity) at low shear and more like a liquid (lowerviscosity) at high shear. As mentioned above, a more viscous swallowchallenge medium 10 provides a more rigorous swallow test that is morelikely to induce manifestation of abnormalities in esophageal motilityin fewer swallow tests than, for example, water or saline solution.Also, test swallows using water may result in a patient showing a 20%rate of ineffective swallow peristalsis, whereas testing the samepatient with a viscous swallow challenge medium, e.g., about 90,000centipoise, may show a higher rate of swallow failures, such as 40%. Inaddition, abnormalities in esophageal motility may be more pronounced inslower bolus transit velocity with a more viscous swallow challengemedium 10 than with water or saline solution, at least in part because amore viscous swallow challenge medium 10 has to be propelled through theesophagus by the peristaltic muscle contractions 20 (FIGS. 1 and 2-6),whereas water may simply gravity flow at a high velocity through theesophagus regardless of the strength or effectiveness or velocity of theperistaltic muscle contractions in the esophagus. However, a constanthigh viscosity material may be difficult for a patient to swallowwithout gagging or psychological resistance to even getting it out ofthe mouth and into the esophagus. A thixotropic swallow challenge medium10 alleviates this problem by feeling and flowing more like a lowviscosity liquid in the initial swallow process, which is a higher shearcondition, and then being more like a high viscosity liquid or solid,once it is in the esophagus where the shear conditions are lower.

[0044] Therefore, in addition to having the high shear viscositycharacteristics described above, it is also desirable to have a higherviscosity in low shear conditions. Consequently, a low shear (0.3 rpm onthe same Brookfield viscometer as that described above) viscosityswallow challenge medium in a range of about 50,000 to 800,000 equipoiseis desirable, preferably about 100,000 to 600,000 equipoise, and morepreferably about 300,000 to 500,0000 equipoise. Also, a medium shear(3.0 rpm on the same Brookfield viscometer as that described above)viscosity for the swallow challenge medium may be in a range of about10,000 to 300,000 equipoise, preferably about 50,000 to 200,000equipoise, and more preferably about 80,000 to 100,000 equipoise. Adecrease in viscosity by, for example, about twenty-fold or more over atwo-decade increase in the rotation velocity of the viscometer spindleis a good thixotropic characteristic.

[0045] The swallow challenge medium of this invention also preferablyhas a high electrical conductivity in contrast to a substantially lowerconductivity of the tissue lining of the esophagus to enable accurateimpedance measurements with equipment such as that described above andto enable a clear, highly detectable drop in impedance when the swallowchallenge medium 10 moves into contact with the sensor electrodes 41-48.For example, the swallow challenge medium preferably has a conductivityof about 4.5 mS/cm to about 7.6 mS/cm. These electrical conductivitiescan be achieved by a sufficiently high ionic density in the swallowchallenge medium 10, and such high ionic density can be achieved andcontrolled by including a proper amount of any food grade ion donors,such as sodium chloride. The ionic density can be controlled at asufficiently high level so that a relatively small amount, such as 5 ml,of the swallow challenging medium 10 produces adequate amount of changein impedance between a pair of electrodes 41-42, 42-43, 43-44, 44-45,45-46, 46-47, 47-48 (FIGS. 1 and 2-6) when the swallow challenge mediumbolus 10 bridges the electrodes to provide a clear reading or indicationof real time swallow challenge medium bolus 10 position in the esophagusby the impedance detector circuits, as described above. With sufficientionic content to get the conductivity of the swallow challenge mediuminto the preferred 4.5 to 7.6 mS/cm range mentioned above, as little as1 ml. of the swallow challenge medium can be detected with a probe thathas impedance sensor electrodes 41-48 spaced as shown in FIG. 1, i.e.,approximately 2.5 cm apart.

[0046] As mentioned above, it is also preferred that the swallowchallenge medium has a very high surface tension so that it does notcoat and cling to the surfaces of the electrodes 41-48 and/or probe 12with enough residue to introduce a significant amount of error in thesubsequent impedance measurements. In other words, it is desirable tonot only have a clear reading of the low impedance presence of theswallow challenge medium bolus 10, when it is present at a particularelectrode or contact pair location, as explained above, but it is alsodesirable to have a clear higher impedance reading from those sameelectrode or contact pairs when the swallow challenge medium bolus 10passes that location. Otherwise, not only will the impedance readingsfrom those electrodes not return to base impedance level and indicatewhen the bolus 10 has moved past those electrodes, they may also not beable to indicate when swallow challenge media from subsequent swallowsarrive at those electrodes. Therefore, it is important to not have theswallow challenge medium 10 that leaves a coating or enough residue onthe surfaces of the electrodes 41-48 and probe 12 to bridge pairs ofelectrodes and carry electric current between them after the bolus ofswallow challenge medium has passed. As mentioned above, a high surfacetension in the swallow challenge medium solves this problem. Highsurface tension is characterized by high cohesive strength, i.e.,attraction to like molecules, and low adhesion, i.e., low or negligibleattraction to unlike molecules. Surface tension of a material inrelation to material-to-electrode surface and material-to-probe surface,instead of conventional material-to-air surface tension parameters, isdifficult to quantify directly. However, in this application, thenon-coating property can be quantified indirectly by comparing impedancemeasured across a pair of electrodes before contact with the swallowchallenge medium with impedance measured across the pair of electrodesafter contact with the swallow challenge medium. For example, it can bedone by first measuring the impedance between a pair of the electrodesor contacts, e.g., electrodes 41-42, on the probe 12 in dry air. Second,immerse the probe 12 and electrodes 41-42 in a sample of the swallowchallenge medium and pull it out of the medium. Third, without wipingthe probe 12 or electrodes 41-42, measuring the impedance again acrossthe electrodes 41-42. If the second impedance measurement afterimmersion and withdrawal of the electrodes from the swallow challengemedium samples is substantially the same as the impedance reading beforethe immersion, the indication is that very little, if any, of theswallow challenge medium sample remained on the probe 12 and electrodes41-42, thus did not stick. For example, a drop of 20% or less inimpedance in this kind of test may be considered an indication of anadequate non-stick characteristic, although a drop of 10% or less ispreferred, and a drop of 1% or less is even more preferred.

[0047] Healthy esophageal tissue lining has an impedance of about 1,000to 3,000 ohms. Therefore, the swallow challenge medium should at leasthave an impedance of about 300 to 600 ohms, when it is diluted withsaliva, which may be slightly higher than the impedance of the swallowchallenge medium itself before it is diluted with saliva from the mouthand esophagus.

[0048] For palatability, sweeteners such as sugar or sucralose, andflavoring agents, such as artificial banana, cherry, grape or pineappleflavors can be included in the swallow challenge medium. Preservativesand mold and yeast inhibitors can also be included to ensure adequateshelf life, for example a year or more. Another attribute of the swallowchallenge medium is its non-allergenic property. All ingredients arefood-grade. Particularly useful for diabetic patients is the variety inwhich sugar is replaced with an artificial sweetener, such as sucralose.

[0049] An example, a swallow challenge medium can be made by firstblending the following ingredients together: Gelcarin GP 539  1.9 gPotassium citrate monohydrate 0.24 g Sodium chloride 0.16 g Sodiumbenzoate 0.15 g Potassium sorbate 0.15 g Sucralose 0.02 g Yellow #50.001 g 

[0050] 140 g of de-ionized water is then added to the blend withvigorous mixing. The resultant slurry is heated to about 50-100° C.,preferably about 70° C., to dissolve the solids. While the solution isstirring, 0.38 g of banana flavor and 0.22 g citric acid can bedissolved in 7 g of de-ionized water to form an acidified flavoringsolution. The heated solution can then be removed from the heat, and theacidified flavoring solution can be added with stirring to disperse itevenly. The mixture can then be decanted into a suitable vessel andcooled before using.

[0051] A swallow challenge medium prepared in this manner was tested forvarious properties. For viscosity measurement, a Brookfield Viscometer,LVT model, with a number-4 spindle was used at three different levels ofshear (spindle velocities). The conductivity and impedance weredetermined by measuring electric current between a pair of electrodes 5cm from each other and submerged in a cylinder of the swallow challengemedium 2 cm in diameter. The pH was also measured. The results arelisted in Table I. TABLE I Property Value Viscosity (centipoises)460,000 at spindle velocity 0.3 rpm  90,000 at spindle velocity 3.0 rpm 13,500 at spindle velocity 30 rpm  Conductivity (mS/cm) 5.7 Impedance(Ohms) 400 pH 4.5

[0052] While a workable swallow challenge medium for some aspects ofthis invention can be within the ranges described above, one aspect ofthis invention is to provide a swallow challenge medium that hassufficiently consistent physical properties to be useable as a reliablestandard swallow challenge medium, for compilation of reliable andmeaningful standards for healthy esophageal motility functions, and formeaningful comparisons of individual esophageal test results to suchstandards. For such a standardizable quality, it is desirable to keepthe physical properties of the swallow challenge medium within 15% ofthose values shown in Table I above, i.e., low shear (Brookfield 0.3rpm) viscosity of 391,000 to 529,000 centipoises, medium shear(Brookfield 3.0 rpm) viscosity of 76,500 to 103,500 centipoises, highshear (Brookfield 30 rpm) viscosity of 11,475 to 15,525 centipoises,conductivity of 4.8 to 6.6 mS/cm, impedance of 340 to 460 ohms, and/orpH of 3.8 to 5.2. These viscosity measurements are based on the sameBrookfield parameters and equipment as described above.

[0053] A prototype and three additional samples were also prepared withsubstantially the same recipe as above, but with sugar rather thansucralose. The characteristics are listed in Table II. TABLE II LowShear (Spindle Medium Shear High Shear Velocity = (Spindle Velocity =(Spindle Velocity = Sample 0.3 RPM) 3.0 RPM) 30 RPM) Prototype 420,00098,000 16,000 1 400,000 90,000 13,000 2 420,000 86,000 12,000 3 420,00086,000 11,000

[0054] The conductivity of the three samples were, respectively, 4.14,4.15 and 4.22 mS/cm. The pH values were, respectively, 4.58, 4.60 and4.60.

[0055] The non-sticking property of a swallow challenge medium preparedin a manner similar to those used in the examples above was measured bymeasuring the impedance between a pair of electrodes on a probe(Sandhill Scientific, Inc., model MII) before and after the electrodeswere immersed four inches deep in the sample swallow challenge medium ina tube of 2.0 cm in diameter without cleaning the probe after removal.The impedance was 11,800 ohms before immersion, 450 ohms duringimmersion, and 11,600 ohms after removal, i.e., a decrease in impedanceof only 0.2% from pre-immersion to post-removal.

[0056] It should be noted that the choice of one or more ingredients forone property may affect one or more other properties of the challengemedium. Thus, to produce a challenge medium with a different combinationof desired properties or to substitute one or more ingredients to obtaina challenge medium with the same set of properties may require multipleiterations of adjustment of ratios of ingredients. Such adjustments,however, are within the competence of persons skilled in the art suchthat he/she will be able to achieve the desired alternative propertiesand/or ingredients without undue experimentation. Also, while thedescription above is made with primary references and illustrationsrelating to the esophagus and esophageal peristalsis and bolus transitdynamics, it is also applicable to the oropharynx and diagnostics ofswallow disorders in the oropharynx. Therefore, rather than repeateverything described and claimed herein for the oropharynx andoropharyngeal bolus transit dynamics the descriptions, references, andclaims of this invention in relation to the esophagus are considered toalso include the oropharynx muscular movements and oropharygeal bolustransits during swallowing.

[0057] The particular embodiments disclosed above are illustrative only,as the invention may be modified and practiced in different butequivalent manners apparent to those skilled in the art having thebenefit of the teachings herein. Furthermore, no limitations areintended to the details of construction or design herein shown, otherthan as described in the claims below. It is therefore evident that theparticular embodiments disclosed above may be altered or modified andall such variations are considered within the scope and spirit of theinvention. Accordingly, the protection sought herein is as set forth inthe claims below.

[0058] The foregoing description is considered as illustrative of theprinciples of the invention. Furthermore, since numerous modificationsand changes will readily occur to those skilled in the art, it is notdesired to limit the invention to the exact construction and processshown and described above. Accordingly, resort may be made to allsuitable modifications and equivalents that fall within the scope of theinvention. The words “comprise,” “comprises,” “comprising,” “include,”“including,” and “includes” when used in this specification are intendedto specify the presence of stated features, integers, components, orsteps, but they do not preclude the presence or addition of one or moreother features, integers, components, steps, or groups thereof.

The embodiments of the invention in which an exclusive property or privilege is claimed are defined as follows:
 1. A challenge medium for assessing the condition of an organ, wherein the challenge medium exhibits a viscosity of about 1,000 centipoise to about 100,000 centipoise, measured at 30 rpm using a Brookfield Viscometer, LVT model, with a number-4 spindle, and an electrical conductivity of about 2.3 mS/cm to about 11 mS/cm, wherein the.
 2. The challenge medium of claim 1, wherein the viscosity ranges from about 5,000 to about 50,000 centipoise.
 3. The challenge medium of claim 1, wherein the viscosity ranges from about 6,000 to about 20,000 centipoise.
 4. The challenge medium of claim 1, wherein the electrical conductivity ranges from about 4.0 to about 7.0 mS/cm.
 5. The challenge medium of claim 1, further being thixotropic.
 6. The challenge medium of claim 5, exhibiting a decrease in viscosity at least by about 20-fold over a two-decade increase in the rotation velocity of the viscometer spindle.
 7. The challenge medium of claim 6, exhibiting a decrease in viscosity at least by about 30-fold over a two-decade increase in the rotation velocity of the viscometer spindle.
 8. The challenge medium of claim 1, further having a pH of about 3.5 to about 9.0.
 9. The challenge medium of claim 8, having a pH of about 4.0 to about 9.0.
 10. The challenge medium of claim 9, having a pH of about 4.5 to about 8.0.
 11. The challenge medium of claim 1, further being substantially non-sticking to stainless steel.
 12. The challenge medium of claim 1, comprising a thickening agent and an ion donor.
 13. The challenge medium of claim 12, wherein the thickening agent comprise a polysaccharide.
 14. The challenge medium of claim 13, wherein the polysaccharide comprises carrageenan.
 15. The challenge medium of claim 12, wherein the ion donor comprises sodium chloride.
 16. The challenge medium of claim 12, further comprising a preservative.
 17. A method of measuring the physiological functions of an organ, the method comprising: introducing a predetermined quantity of a challenge medium into the organ; selecting a plurality of pairs of locations along a path in the organ; measuring the impedance between each pair of positions; and determining the location of the challenge medium along the path as a function of time.
 18. The method of claim 17, wherein the step of introducing a challenge medium comprises introducing a challenge medium exhibiting a viscosity of about 1,000 centipoise to about 100,000 centipoise, measured at 30 rpm using a Brookfield Viscometer, LVT model, with a number-4 spindle, and an electrical conductivity of about 2.3 mS/cm) to about 11 mS/cm.
 19. The method of claim 18, further comprising determining the pressures at a plurality of locations along the path in the organ as a function of time and comparing the location of the challenge medium along the path with pressure along the path as a function of time.
 20. The method of claim 19, further comprising repeating the steps therein a plurality of times and comparing the results with a standard.
 21. A method of testing peristalsis and bolus transit in a person's esophagus comprising: positioning a probe comprising a plurality of electrodes in longitudinally spaced relation to each other in the person's esophagus; having the person swallow a swallow challenge medium that has viscosity in a range of 1,000 to 100,000 centipoise (high shear), conductivity in the range of 3.8 to 7.6 mS/cm, and sufficient surface tension to cause the swallow challenge medium to clear sufficiently from surfaces of the electrodes and probe as the swallow challenge medium passes the electrodes and probe such that impedance measurements across the electrodes after the swallow challenge medium passes the electrodes is not less than 50% of impedance measurements across the electrodes before the challenge medium reaches the electrodes; measuring impedance across the electrodes on a real time basis as the challenge medium moves though the esophagus, and recording the impedance measurements as a function of time.
 22. The method of claim 21, wherein the surface tension is sufficient such that said drop in impedance is not more than 1%.
 23. The method of claim 21, wherein the swallow challenge medium is thixotropic.
 24. The method of claim 21, wherein the swallow challenge medium has conductivity in a range of 4.5 to 7.6 mS/cm.
 25. The method of claim 21, wherein the swallow challenge medium provides impedance in a range of 300 to 600 ohms.
 26. The method of claim 21, wherein the swallow challenge medium provides impedance in a range of 300 to 500 ohms.
 27. The method of claim 21, wherein the swallow challenge medium has pH in a range of 3.5 to 9.0.
 28. A method of testing peristalsis and bolus transit in a person's esophagus, comprising: positioning a plurality of electrodes in longitudinally spaced relation to each other in a person's esophagus; having the person swallow a thixotropic swallow challenge medium that has low shear viscosity in a range of 391,000 to 529,000 centipoises, medium shear viscosity in a range of 76,500 to 103,500 centipoises, and high shear viscosity in a range of 11,475 to 15,525 centipoises; and measuring impedance across the electrodes as the swallow challenge medium moves through the esophagus.
 29. The method of claim 28, wherein the swallow challenge medium has conductivity in a range of 4.8 to 6.6 mS/cm.
 30. The method of claim 28, wherein the swallow challenge medium has an impedance in a range of 340 to 460 ohms.
 31. The method of claim 28, wherein the swallow challenge medium has pH in a range of 3.8 to 5.2.
 32. A swallow challenge medium comprising a thixotropic material having a low shear viscosity in a range of 391,000 to 529,000 centipoises, a medium shear viscosity in a range of 76,500 to 103,500 centipoises, and a high shear viscosity in a range of 11,475 to 15,525 centipoises.
 33. The swallow challenge material of claim 32, wherein the material also has conductivity in a range of 4.8 to 6.6 mS/cm.
 34. The swallow challenge material of claim 32, wherein the material also has impedance in a range of 340 to 460 ohms.
 35. The swallow challenge material of claim 32, wherein the material also has pH in a range of 3.8 to 5.2. 